University of Lyon, CNRS, UMR5086 "Molecular Microbiology and Structural Biochemistry", IBCP, 7 Passage du Vercors, F-69367, Lyon, France.
Institut de Biologie Structurale (IBS), University Grenoble Alpes, CEA, CNRS, 38044, Grenoble, France.
Sci Rep. 2018 Feb 2;8(1):2309. doi: 10.1038/s41598-018-20558-z.
During the evolution of cellular bioenergetics, many protein families have been fashioned to match the availability and replenishment in energy supply. Molecular motors and primary transporters essentially need ATP to function while proteins involved in cell signaling or translation consume GTP. ATP-Binding Cassette (ABC) transporters are one of the largest families of membrane proteins gathering several medically relevant members that are typically powered by ATP hydrolysis. Here, a Streptococcus pneumoniae ABC transporter responsible for fluoroquinolones resistance in clinical settings, PatA/PatB, is shown to challenge this concept. It clearly favors GTP as the energy supply to expel drugs. This preference is correlated to its ability to hydrolyze GTP more efficiently than ATP, as found with PatA/PatB reconstituted in proteoliposomes or nanodiscs. Importantly, the ATP and GTP concentrations are similar in S. pneumoniae supporting the physiological relevance of GTP as the energy source of this bacterial transporter.
在细胞生物能量学的进化过程中，许多蛋白质家族被塑造出来以适应能量供应的可用性和补充。分子马达和主要转运蛋白本质上需要 ATP 才能发挥作用，而参与细胞信号转导或翻译的蛋白质则消耗 GTP。ATP 结合盒（ABC）转运蛋白是膜蛋白最大的家族之一，其中包含许多与医学相关的成员，这些成员通常由 ATP 水解提供动力。在这里，一种与临床环境中氟喹诺酮类药物耐药性有关的肺炎链球菌 ABC 转运蛋白 PatA/PatB 被证明挑战了这一概念。它明显更喜欢 GTP 作为能量供应来排出药物。这种偏好与它水解 GTP 的效率比 ATP 更高的能力相关，这在重组到脂质体或纳米盘中的 PatA/PatB 中得到了发现。重要的是，肺炎链球菌中的 ATP 和 GTP 浓度相似，支持 GTP 作为这种细菌转运蛋白的能量来源的生理相关性。
